Finally, since (1) there is clear evidence for circuit hyperactivity at early stages in various AD mouse models (reviewed in ref. 64), (2) increased neuronal activity is sufficient to activate AMPK in a CAMKK2-dependent manner2, and (3) amyloidogenic APP processing into Aβ42 is activity-dependent65, we tested if part of the protective effect of reducing AMPK in the context of AD pathophysiology could be due to decreased APP processing and Aβ42 production. Here, PRKAA1 is linked to Alzheimer disease.